Perseveration and shifting in Obsessive-Compulsive Disorder as a function of uncertainty, punishment, and Serotonergic medication

Apergis-Schoute, A.M. and van der Flier, F.E. and Ip, S.H.Y. and Kanen, J.W. and Vaghi, Matilde M. and Fineberg, N.A. and Sahakian, B. J. and Cardinal, R.N. and Robbins, T.W. (2024) Perseveration and shifting in Obsessive-Compulsive Disorder as a function of uncertainty, punishment, and Serotonergic medication. Biological Psychiatry Global Open Science 4 (1), pp. 326-335. ISSN 2667-1743.

Abstract

Background: The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD. Methods: We recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with uncertain feedback and a single reversal measuring win-stay and lose-shift. Bayesian computational modeling provided measures of learning rate, reinforcement sensitivity, and stimulus stickiness. Results: Unmedicated patients with OCD were impaired on the deterministic reversal task under punishment only at the first and third reversals compared with both control participants and medicated patients with OCD, who had no deficit. Perseverative errors were correlated with OCD severity. On the probabilistic reversal task, unmedicated patients were only impaired at reversal, whereas medicated patients were impaired at both the learning and reversal stages. Computational modeling showed that the overall change was reduced feedback sensitivity in both OCD groups. Conclusions: Both perseveration and increased shifting can be observed in OCD, depending on test conditions including the predictability of reinforcement. Perseveration was related to clinical severity and remediated by serotonergic medication.

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